Use of Antibiotics and Risk of Psychiatric Disorders in Newly Diagnosed Cancer Patients: A Population-Based Cohort Study in Sweden

Author:

Hu Kejia1ORCID,Smedby Karin E.2,Sjölander Arvid3,Montgomery Scott456ORCID,Valdimarsdóttir Unnur37ORCID,Engstrand Lars8ORCID,Fang Fang1ORCID,Fall Katja14ORCID

Affiliation:

1. 1Unit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

2. 2Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

3. 3Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

4. 4Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden.

5. 5Clinical Epidemiology Division, Department of Medicine, Karolinska Institutet, Solna, Sweden.

6. 6Department of Epidemiology and Public Health, University College London, London, United Kingdom.

7. 7Centre of Public Health Sciences Faculty of Medicine, University of Iceland, Reykjavík, Iceland.

8. 8Center for Translational Microbiome Research, Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Science for Life Laboratory, Solna, Sweden.

Abstract

Abstract Background: Antibiotic-induced dysbiosis is associated with an increased risk of depression and anxiety in the general population. A diagnosis of cancer is associated with an immediately and dramatically elevated risk of psychiatric disorders, but the potential influence of prediagnostic antibiotic-induced dysbiosis is unknown. Methods: Based on a national cohort of cancer patients in Sweden, we included 309,419 patients who were diagnosed with a first primary malignancy between July 2006 and December 2013. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of first-onset psychosis, depression, anxiety, or stress-related disorders during the first year after cancer diagnosis for antibiotic use during the year before cancer diagnosis. Results: Compared with no antibiotic use, use of antibiotics was associated with a higher rate of the aforementioned psychiatric disorders (HR, 1.23; 95% CI, 1.16–1.30) after adjustment for sociodemographic factors, comorbidity, potential indications for antibiotics, and cancer stage and type. The magnitude of the association was higher for broad-spectrum antibiotics (HR, 1.27; 95% CI, 1.18–1.37), higher doses (HR, 1.32; 95% CI, 1.22–1.44), more frequent use (HR, 1.33; 95% CI, 1.21–1.46), and recent use (HR, 1.26; 95% CI, 1.17–1.35). Conclusions: Use of antibiotics, especially of broad-spectrum type, of high dose and frequency, with recent use, was associated with an aggravated risk of psychiatric disorders, compared with no antibiotic use. Impact: A better understanding of the microbiota–gut–brain axis may open up a wide avenue for the prevention and treatment of psychiatric disorders in cancer patients.

Funder

China Scholarship Council

Swedish Cancer Society

Swedish Research Council for Health, Working Life and Welfare

Publisher

American Association for Cancer Research (AACR)

Subject

Oncology,Epidemiology

Reference34 articles.

1. The gut microbiome in neurological disorders;Cryan,2020

2. The central nervous system and the gut microbiome;Sharon;Cell. Cell Press,2016

3. Recovery of gut microbiota of healthy adults following antibiotic exposure;Palleja;Nat Microbiol,2018

4. Antibiotics and the human gut microbiome: dysbioses and accumulation of resistances;Francino;Front Microbiol,2016

5. The microbiota–gut–brain axis;Cryan;Physiol Rev,2019

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